The global burden of dengue is large with an estimated 50 million infections per year occurring across 100 countries. Puerto Rico, a Commonwealth of the USA, has the largest US population with endemic dengue. The island offers a unique opportunity to study the epidemiology, outcomes and prevention of dengue, as well as its clinical presentation and how dengue can be differentiated from other Acute Febrile Illnesses (AFI), such as chikungunya, transmitted by the same vector. The Saint Luke's Episcopal Hospital and Ponce School of Medicine Consortium has implemented a Sentinel Enhanced Dengue Surveillance System (SEDSS) through a Cooperative Agreement with the CDC that serves as a model of enhanced surveillance and an effective research platform to conduct studies on dengue and other AFI. Lessons learned from SEDSS implementation have been applied to this proposal to support and improve on the current enhanced surveillance site and to build on its strengths. The new project: Sentinel Enhanced Dengue Surveillance System to Evaluate Dengue Epidemiology, Outcomes and Prevention (SEDSS-EDEOP) will work to sustain the interest and commitment of hospital's administration, foster collaboration between the medical school, the public health program, the hospital and the community, as well as develop research capacity in medical residents, and medical and public health students that will create the future of dengue research in Puerto Rico. In addition to enhanced surveillance, the SEDSS-EDEOP Project will develop a comparative effectiveness research program to study dengue management strategies in a real world setting. This program should yield information on best practices that can be applied by clinicians to improve dengue outcomes. The SEDSS-EDEOP Project is likely to result in a model of enhanced epidemiologic surveillance and a strong research platform for studying dengue and AFI and the impact of primary and secondary dengue prevention strategies.